Titanium dioxide nanoparticles promote oxidative stress, autophagy and reduce NLRP3 in primary rat astrocytes
Por:
Pérez-Arizti J.A., Ventura-Gallegos J.L., Galvan Juarez, Roberto Erasmo, Ramos-Godinez M.D.P., Colin-Val, Zaira, Lopez-Marure, Rebeca
Publicada:
1 ene 2020
Resumen:
Titanium dioxide nanoparticles (TiO2-NPs) are widely used in the food industry, cosmetics, personal care and paints among others. Through occupational exposure and daily consumption, and because of their small size, TiO2-NPs can enter the body through different routes such as oral, dermal and inhalation, and accumulate in multiple organs including the brain. TiO2-NPs cause severe damage to many cell types, however their effects in the central nervous system remain largely unexplored. Therefore, in the present study we determined the cytotoxic effect of TiO2-NPs on rat astrocytes. We tested the oxidant properties of TiO2-NPs through DTT depletion, and measured oxidative stress-induced damage in mitochondria, through oxidation of 2,7-dichlorodihydrofluorescein diacetate (H2DCFDA) and loss of mitochondrial membrane potential ( ?m) with Mitotracker Green FM. We further examined oxidative stress-derived responses such as I?B-a degradation by Western Blot, NF-?B translocation by EMSA, autophagy induction by LC3-II levels, and expression of the inflammasome protein NLRP3. TiO2-NPs showed high oxidant properties and induced strong oxidative stress in astrocytes following their internalization, causing mitochondrial damage detected by ?m loss. Responses against oxidative damage such as NF-?B translocation and autophagy were induced and NLRP3 protein expression was downregulated, indicating lower inflammasome-mediated responses in astrocytes. These results support TiO2-NPs cytotoxicity in astrocytes, cells that play key roles in neuronal homeostasis and their dysfunction can lead to neurological disorders including cognitive impairment and memory loss. © 2020 Elsevier B.V.
Filiaciones:
Pérez-Arizti J.A.:
Departamento de Fisiología, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico
Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico
Ventura-Gallegos J.L.:
Departamento de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Mexico
Departamento de Medicina Genómica y Toxicología Ambiental IIB, Universidad Nacional Autónoma de México, Mexico
Galvan Juarez, Roberto Erasmo:
Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Mexico
CINVESTAV, IPN, Ctr Invest & Estudios Avanzados, Dept Toxicol, Mexico City, DF, Mexico
Ramos-Godinez M.D.P.:
Departamento de Microscopía Electrónica, Instituto Nacional de Cancerología, Ciudad de México, Mexico
Colin-Val, Zaira:
Departamento de Fisiología, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico
Inst Nacl Cardiol Ignacio Chavez, Dept Fisiol, Mexico City, DF, Mexico
Lopez-Marure, Rebeca:
Departamento de Fisiología, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico
Inst Nacl Cardiol Ignacio Chavez, Dept Fisiol, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Med, Mexico City, DF, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Bioquim, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Dept Med Genom & Toxicol Ambiental IIB, Mexico City, DF, Mexico
Inst Nacl Cancerol, Dept Microscopia Elect, Ciudad De Mexico, Mexico
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